Effectiveness of MRNA booster vaccine among healthcare workers in New York City during the Omicron surge,December 2021 to January 2022

ObjectiveTo describe effectiveness of mRNA vaccines by comparing 2-dose (2D) and 3-dose (3D) healthcare worker (HCW) recipients in the setting of Omicron variant dominance. Performance of 2D and 3D vaccine series against SARS-CoV-2 variants and the clinical outcomes of HCWs may inform return-to-work guidance.MethodsIn a retrospective study from December 15, 2020 to January 15, 2022, SARS-CoV-2 infections among HCWs at a large tertiary cancer centre in New York City were examined to estimate infection rates (aggregated positive tests / person-days) and 95% CIs over the Omicron period in 3D and 2D mRNA vaccinated HCWs and were compared using rate ratios. We described the clinical features of post-vaccine infections and impact of prior (pre-Omicron) COVID infection on vaccine effectiveness.ResultsAmong the 20857 HCWs in our cohort, 20,660 completed the 2D series with an mRNA vaccine during our study period and 12461 had received a third dose by January 15, 2022. The infection rate ratio for 3D versus 2D vaccinated HCWs was 0.667 (95% CI 0.623, 0.713) for an estimated 3D vaccine effectiveness of 33.3% compared to two doses only during the Omicron dominant period from December 15, 2021 to January 15, 2022. Breakthrough Omicron infections after 3D + 14 days occurred in 1,315 HCWs. Omicron infections were mild, with 16% of 3D and 11% 2D HCWs being asymptomatic.DiscussionStudy demonstrates improved vaccine-derived protection against COVID-19 infection in 3D versus 2D mRNA vaccinees during the Omicron surge. The advantage of 3D vaccination was maintained irrespective of prior COVID-19 infection status.     

Evidence of co-infections during Delta and Omicron SARS-CoV-2 variants co-circulation through prospective screening and sequencing

ObjectivesTo describe Delta/Omicron SARS-CoV-2 variants co-infection detection and confirmation during the fifth wave of COVID-19 pandemics in France in 7 immunocompetent and epidemiologically unrelated patients.MethodsSince December 2021, the surveillance of Delta/Omicron SARS-CoV-2 variants of concern (VOC) circulation was performed through prospective screening of positive-samples using single nucleotide polymorphism (SNP) PCR assays targeting SARS-CoV-2 S-gene mutations K417N (Omicron specific) and L452R (Delta specific). Samples showing unexpected mutational profiles were further submitted to whole genome sequencing (WGS) using three different primer sets.ResultsBetween weeks 49-2021 and 02-2022, SARS-CoV-2 genome was detected in 3831 respiratory samples, of which 3237 (84.5%) were screened for VOC specific SNPs. Unexpected mutation profiles suggesting a dual Delta/Omicron population were observed in 7 nasopharyngeal samples (0.2%). These co-infections were confirmed by WGS. For 2 patients, the sequence analyses of longitudinal samples collected 7 to 11 days apart showed that Delta or Omicron can outcompete the other variant during dual infection. Additionally, for one of these samples, a recombination event between Delta and Omicron was detected.ConclusionsThis work demonstrates that SARS-CoV-2 Delta/Omicron co-infections are not rare in high virus co-circulation periods. Moreover, co-infections can further lead to genetic recombination which may generate new chimeric variants with unpredictable epidemic or pathogenic properties that could represent a serious health threat.     

Length of hospital stay and risk of intensive care admission and in-hospital death among COVID-19 patients in Norway: a register-based cohort study comparing patients fully vaccinated with an mRNA vaccine to unvaccinated patients

ObjectivesWe estimated the length of stay (LoS) in hospital and the intensive care unit (ICU) and risk of admission to ICU and in-hospital death among COVID-19 patients ≥18 years in Norway who had been fully vaccinated with an mRNA vaccine (at least two doses or one dose and previous SARS-CoV-2 infection), compared to unvaccinated patients.MethodsUsing national registry data, we analyzed SARS-CoV-2–positive patients hospitalized in Norway between 1 February and 30 November 2021, with COVID-19 as the main cause of hospitalization. We ran Cox proportional hazards models adjusting for vaccination status, age, sex, county of residence, regional health authority, date of admission, country of birth, virus variant, and underlying risk factors.ResultsWe included 716 fully vaccinated patients (crude overall median LoS: 5.2 days; admitted to ICU: 103 (14%); in-hospital death: 86 (13%)) and 2487 unvaccinated patients (crude overall median LoS: 5.0 days; admitted to ICU: 480 (19%); in-hospital death: 102 (4%)). In adjusted models, fully vaccinated patients had a shorter overall LoS in hospital (adjusted log hazard ratios (aHR) for discharge: 1.61, 95% CI: 1.24–2.08), shorter LoS without ICU (aHR: 1.27, 95% CI: 1.07–1.52), and lower risk of ICU admission (aHR: 0.50, 95% CI: 0.37–0.69) compared to unvaccinated patients. We observed no difference in the LoS in ICU or in risk of in-hospital death between fully vaccinated and unvaccinated patients.DiscussionFully vaccinated patients hospitalized with COVID-19 in Norway have a shorter LoS and lower risk of ICU admission than unvaccinated patients. These findings can support patient management and ongoing capacity planning in hospitals.     

Comparison of secondary attack rate and viable virus shedding between patients with SARS-CoV-2 Delta and Omicron variants: A prospective cohort study

There are limited data comparing the transmission rates and kinetics of viable virus shedding of the Omicron variant to those of the Delta variant. We compared these rates in hospitalized patients infected with Delta and Omicron variants. We prospectively enrolled adult patients with COVID-19 admitted to a tertiary care hospital in South Korea between September 2021 and May 2022. Secondary attack rates were calculated by epidemiologic investigation, and daily saliva samples were collected to evaluate viral shedding kinetics. Genomic and subgenomic SARS-CoV-2 RNA was measured by PCR, and virus culture was performed from daily saliva samples. A total of 88 patients with COVID-19 who agreed to daily sampling and were interviewed, were included. Of the 88 patients, 48 (59%) were infected with Delta, and 34 (41%) with Omicron; a further 5 patients gave undetectable or inconclusive RNA PCR results and 1 was suspected of being coinfected with both variants. Omicron group had a higher secondary attack rate (31% [38/124] vs. 7% [34/456], p < 0.001). Survival analysis revealed that shorter viable virus shedding period was observed in Omicron variant compared with Delta variant (median 4, IQR [1−7], vs. 8.5 days, IQR [5–12 days], p < 0.001). Multivariable analysis revealed that moderate-to-critical disease severity (HR: 1.96), and immunocompromised status (HR: 2.17) were independent predictors of prolonged viral shedding, whereas completion of initial vaccine series or first booster-vaccinated status (HR: 0.49), and Omicron infection (HR: 0.44) were independently associated with shorter viable virus shedding. Patients with Omicron infections had higher transmission rates but shorter periods of transmissible virus shedding than those with Delta infections.     

Duration of infectious shedding of SARS-CoV-2 Omicron variant and its relation with symptoms

ObjectivesSARS-CoV-2 infections with Omicron variants have a high capability of human-to-human transmission. Nevertheless, the duration of isolation for mild cases was shortened to 5 to 7 days. We aimed to detect the duration of viral shedding among healthcare workers (HCWs) with Omicron by using viral culture.MethodsWe prospectively included newly diagnosed nonsevere, symptomatic SARS-CoV-2 positive HCWs. Nasopharyngeal swab samples were obtained consecutively on days 5, 7,10, and 14 of onset of symptoms. The samples were examined by nucleic acid amplification test and viral culture.ResultsIn total, 55 non-severe patients with SARS-CoV-2 Omicron variant were included. The mean age of the population was 34 years (range, 23 to 54) and 78% (43/55) were female. The PCR positivity rate on days 5, 7, 10, and 14 was 96.4% (53/55), 87.3% (48/55), 74.545% (41/55), and 41.8% (23/55) consecutively, whereas the viral culture positivity rates were 83% (44/53), 52% (26/50), 13.5% (7/52), and 8% (4/50). Among the patients who became symptom-free, the viral culture positivity rates were 100% (4/4), 58% (7/12), 11% (3/27), and 5% (2/41).DiscussionWe showed that among the SARS-CoV-2 Omicron variant infected patients, viral shedding continues for ≥10 days in 13.5% of all cases and 11% in symptom-free cases. The decision for cessation of isolation according to the presence of symptoms could be reconsidered until further studies disapprove of our results. Meanwhile, the infected HCWs who give care to high-risk patients for severe COVID-19 might extend their isolations ≤10 days after the onset of symptoms, regardless of their symptoms.     

Virological and serological kinetics of SARS-CoV-2 Delta variant vaccine breakthrough infections: a multicentre cohort study

ObjectivesHighly effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been developed but variants of concerns are worrisome, especially B.1.617.2 (Delta) which has rapidly spread across the world. We aim to study if vaccination alters virological and serological kinetics in breakthrough infections.MethodsWe conducted a multicentre retrospective cohort study of patients in Singapore who had received a licensed mRNA vaccine and been admitted to hospital with B.1.617.2 SARS-CoV-2 infection. We compared clinical features, virological and serological kinetics (anti-nucleocapsid, anti-spike and surrogate virus neutralization titres) between fully vaccinated and unvaccinated individuals.ResultsOut of 218 individuals with B.1.617.2 infection, 84 received an mRNA vaccine of which 71 were fully vaccinated, 130 were unvaccinated and four received a non-mRNA vaccine. Despite significantly older age in the vaccine breakthrough group, only 2.8% (2/71) developed severe COVID-19 requiring oxygen supplementation compared with 53.1% (69/130) in the unvaccinated group (p < 0.001). Odds of severe COVID-19 following vaccination were significantly lower (adjusted odds ratio 0.07 95% CI 0.015–0.335, p 0.001). PCR cycle threshold values were similar between vaccinated and unvaccinated groups at diagnosis, but viral loads decreased faster in vaccinated individuals. Early, robust boosting of anti-spike protein antibodies was observed in vaccinated patients; however, these titres were significantly lower against B.1.617.2 than the wildtype vaccine strain.DiscussionThe mRNA vaccines are highly effective at preventing symptomatic and severe COVID-19 associated with B.1.617.2 infection. Vaccination is associated with faster decline in viral RNA load and a robust serological response. Vaccination remains a key strategy for control of the COVID-19 pandemic.     

Omicron-specific mRNA vaccine induced cross-protective immunity against ancestral SARS-CoV-2 infection with low neutralizing antibodies

The major challenge in COVID-19 vaccine effectiveness is immune escape by SARS-CoV-2 variants. To overcome this, an Omicron-specific messenger RNA (mRNA) vaccine was designed. The extracellular domain of the spike of the Omicron variant was fused with a modified GCN4 trimerization domain with low immunogenicity (TSomi). After immunization with TSomi mRNA in hamsters, animals were challenged with SARS-CoV-2 virus. The raised nonneutralizing antibodies or cytokine secretion responses can recognize both Wuhan S and Omicron S. However, the raised antibodies neutralized SARS-CoV-2 Omicron virus infection but failed to generate Wuhan virus neutralizing antibodies. Surprisingly, TSomi mRNA immunization protected animals from Wuhan virus challenge. These data indicated that non-neutralizing antibodies or cellular immunity may play a more important role in vaccine-induced protection than previously believed. Next-generation COVID-19 vaccines using the Omicron S antigen may provide sufficient protection against ancestral or current SARS-CoV-2 variants.     

SARS-CoV-2 infection in children evaluated in an ambulatory setting during Delta and Omicron time periods

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and re-emergence of other respiratory viruses highlight the need to understand the presentation of and factors associated with SARS-CoV-2 in pediatric populations over time. The objective of this study was to evaluate the sociodemographic characteristics, symptoms, and epidemiological risk factors associated with ambulatory SARS-CoV-2 infection in children and determine if factors differ by variant type. We conducted a retrospective cohort study of outpatient children undergoing SARS-CoV-2 polymerase chain reaction testing between November 2020 and January 2022. Test-positive were compared with test-negative children to evaluate symptoms, exposure risk, demographics, and comparisons between Omicron, Delta, and pre-Delta time periods. Among 2264 encounters, 361 (15.9%) were positive for SARS-CoV-2. The cohort was predominantly Hispanic (51%), 5–11 years (44%), and 53% male; 5% had received two coronavirus disease 2019 (COVID-19) vaccine doses. Factors associated with a positive test include loss of taste/smell (adjusted odds ratio [aOR]: 6.71, [95% confidence interval, CI: 2.99–15.08]), new cough (aOR: 2.38, [95% CI: 1.69–3.36]), headache (aOR: 1.90, [95% CI: 1.28–2.81), fever (aOR: 1.83, [95% CI: 1.29–2.60]), contact with a positive case (aOR: 5.12, [95% CI: 3.75–6.97]), or household contact (aOR: 2.66, [95% CI: 1.96–3.62]). Among positive children, loss of taste/smell was more predominant during the Delta versus Omicron and pre-Delta periods (12% vs. 2% and 3%, respectively, p = 0.0017), cough predominated during Delta/Omicron periods more than the pre-Delta period (69% and 65% vs. 41%, p = 0.0002), and there were more asymptomatic children in the pre-Delta period (30% vs. 18% and 10%, p = 0.0023). These findings demonstrate that the presentation of COVID-19 in children and most susceptible age groups has changed over time.     

Challenges of SARS-CoV-2 Omicron Variant and appropriate countermeasures

The Omicron (B.1.1.529) variant was first reported in South Africa and rapidly spread worldwide in early November 2021. This caused panic in various countries, so it is necessary to understand Omicron Variant. This paper summarizes omicron variant-related research achievements. Studies have shown that Omicron Variant contains many mutations that make it more infectious and transmissible. At the same time, immune escape is also caused, resulting in reduced efficacy of existing vaccines, increased risk of reinfection, treatment failure or reduction of monoclonal antibody therapies, and detection failure. However, current data indicate that Omicron Variant causes mild clinical symptoms and few severe cases and deaths. Omicron Variant is valid for a range of nonpharmaceutical interventions against SARS-CoV-2. Improving diagnostic accuracy and enabling timely isolation and treatment of diagnosed cases is also critical to interrupting the spread of omicron variants. COVID-19 vaccine boosters could undoubtedly help control Omicron spread and infection. However, developing a vaccine specific to Omicron Variant is also imminent.     

Current immunoassays and detection of antibodies elicited by Omicron SARS-CoV-2 infection

The present study aimed to determine whether current commercial immunoassays are adequate for detecting anti-Omicron antibodies. We analyzed the anti-SARS-CoV-2 antibody response of 23 unvaccinated individuals 1–2 months after an Omicron infection. All blood samples were tested with a live virus neutralization assay using a clinical Omicron BA.1 strain and four commercial SARS-CoV-2 immunoassays. We assessed three anti-Spike immunoassays (SARS-CoV-2 IgG II Quant [Abbott S], Wantaï anti-SARS-CoV-2 antibody ELISA [Wantaï], Elecsys Anti-SARS-CoV-2 S assay [Roche]) and one anti-Nucleocapsid immunoassay (Abbott SARS-CoV-2 IgG assay [Abbott N]). Omicron neutralizing antibodies were detected in all samples with the live virus neutralization assay. The detection rate of the Abbott S, Wantai, Roche, and Abbott N immunoassays were 65.2%, 69.6%, 86.9%, and 91.3%, respectively. The sensitivities of Abbott S and Wantai immunoassays were significantly lower than that of the live virus neutralization assay (p = 0.004, p = 0.009; Fisher's exact test). Antibody concentrations obtained with anti-S immunoassays were correlated with Omicron neutralizing antibody concentrations. These data provide clinical evidence of the loss of performance of some commercial immunoassays to detect antibodies elicited by Omicron infections. It highlights the need to optimize these assays by adapting antigens to the circulating SARS-CoV-2 strains.     

Differences in incidence and fatality of COVID-19 by SARS-CoV-2 Omicron variant versus Delta variant in relation to vaccine coverage: A world-wide review

We aim to evaluate the evolution differences in the incidence and case fatality rate (CFR) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants. The average incidence and CFRs were described between different countries. A gamma generalized linear mixed model (GLMM) was used to compare the CFRs of Delta and Omicron variants based on vaccination coverage. Totally, 50 countries were included for analyses. The incidence of coronavirus disease 2019 (COVID-19) ranged from 0.16/100,000 to 82.95/100,000 during the Delta period and 0.03/100,000 to 440.88/100,000 during the Omicron period. The median CFRs were 8.56 (interquartile range [IQR]: 4.76–18.39) during the Delta period and 3.04 (IQR: 1.87–7.48) during the Omicron period, respectively. A total of 47 out of 50 countries showed decreased CFRs of the Omicron variant with the rate ratio ranging from 0.02 (95% confidence interval [CI]: 0.01–0.03) (in Cambodia) to 0.97 (95% CI: 0.87–1.08) (in Ireland). Gamma GLMM analysis showed that the decreased CFR was largely a result of the decreased pathogenicity of Omicron besides the increased vaccination coverage. The Omicron variant shows a higher incidence but a lower CFR around the world as a whole, which is mainly a result of the decreased pathogenicity by SARS-CoV-2's mutation, while the vaccination against SARS-CoV-2 still acts as a valuable measure in preventing people from death.     

Molecular evolution of SARS-CoV-2 from December 2019 to August 2022

Severe acute respiratorysyndrome coronavirus-2 (SARS-CoV-2) pandemic spread rapidly and this scenario is concerning worldwide, presenting more than 590 million coronavirus disease 2019 cases and 6.4 million deaths. The emergence of novel lineages carrying several mutations in the spike protein has raised additional public health concerns worldwide during the pandemic. The present study review and summarizes the temporal spreading and molecular evolution of SARS-CoV-2 clades and variants worldwide. The evaluation of these data is important for understanding the evolutionary histories of SARSCoV-2 lineages, allowing us to identify the origins of each lineage of this virus responsible for one of the biggest pandemics in history. A total of 2897 SARS-CoV-2 whole-genome sequences with available information from the country and sampling date (December 2019 to August 2022), were obtained and were evaluated by Bayesian approach. The results demonstrated that the SARS-CoV-2 the time to the most recent common ancestor (tMRCA) in Asia was 2019-12-26 (highest posterior density 95% [HPD95%]: 2019-12-18; 2019-12-29), in Oceania 2020-01-24 (HPD95%: 2020-01-15; 2020-01-30), in Africa 2020-02-27 (HPD95%: 2020-02-21; 2020-03-04), in Europe 2020-02-27 (HPD95%: 2020-02-20; 2020-03-06), in North America 2020-03-12 (HPD95%: 2020-03-05; 2020-03-18), and in South America 2020-03-15 (HPD95%: 2020-03-09; 2020-03-28). Between December 2019 and June 2020, 11 clades were detected (20I [Alpha] and 19A, 19B, 20B, 20C, 20A, 20D, 20E [EU1], 20F, 20H [Beta]). From July to December 2020, 4 clades were identified (20J [Gamma, V3], 21 C [Epsilon], 21D [Eta], and 21G [Lambda]). Between January and June 2021, 3 clades of the Delta variant were detected (21A, 21I, and 21J). Between July and December 2021, two variants were detected, Delta (21A, 21I, and 21J) and Omicron (21K, 21L, 22B, and 22C). Between January and June 2022, the Delta (21I and 21J) and Omicron (21K, 21L, and 22A) variants were detected. Finally, between July and August 2022, 3 clades of Omicron were detected (22B, 22C, and 22D). Clade 19A was first detected in the SARS-CoV-2 pandemic (Wuhan strain) with origin in 2019-12-16 (HPD95%: 2019-12-15; 2019-12-25); 20I (Alpha) in 2020-11-24 (HPD95%: 2020-11-15; 2021-12-02); 20H (Beta) in 2020-11-25 (HPD95%: 2020-11-13; 2020-11-29); 20J (Gamma) was 2020-12-21 (HPD95%: 2020-11-05; 2021-01-15); 21A (Delta) in 2020-09-20 (HPD95%: 2020-05-17; 2021-02-03); 21J (Delta) in 2021-02-26 (2020-11-02; 2021-04-24); 21M (Omicron) in 2021-01-25 (HPD95%: 2020-09-16; 2021-08-08); 21K (Omicron) in 2021-07-30 (HPD95%: 2021-05-30; 2021-10-19); 21L (Omicron) in 2021-10-03 (HPD95%: 2021-04-16; 2021-12-23); 22B (Omicron) in 2022-01-25 (HPD95%: 2022-01-10; 2022-02-05); 21L in 2021-12-20 (HPD95%: 2021-05-16; 2021-12-31). Currently, the Omicron variant predominates worldwide, with the 21L clade branching into 3 (22A, 22B, and 22C). Phylogeographic data showed that Alpha variant originated in the United Kingdom, Beta in South Africa, Gamma in Brazil, Delta in India, Omicron in South Africa, Mu in Colombia, Epsilon in the United States of America, and Lambda in Peru. The COVID-19 pandemic has had a significant impact on global health worldwide and the present study provides an overview of the molecular evolution of SARS-CoV-2 lineage clades (from the Wuhan strain to the currently circulating lineages of the Omicron).     

Impact of combination preventative interventions on hospitalization and death under the pandemic of SARS-CoV-2 Omicron variant in China

With a large population most susceptible to Omicron and emerging SARS-CoV-2 variants, China faces uncertain scenarios if reopening its border. Thus, we aimed to predict the impact of combination preventative interventions on hospitalization and death. An age-stratified susceptible-infectious-quarantined-hospitalized-removed-susceptible (SIQHRS) model based on the new guidelines of COVID-19 diagnosis and treatment (the ninth edition) was constructed to simulate the transmission dynamics of Omicron within 365 days. At baseline, we assumed no interventions other than 60% booster vaccination in individuals aged ≤60 years and 80% in individuals aged >60 years, quarantine and hospitalization. Oral antiviral medications for COVID-19 and nonpharmaceutical interventions (NPIs) such as social distancing and antigen self-testing were considered in subsequent scenarios. Sensitivity analyses were conducted to reflect different levels of interventions. A total of 0.73 billion cumulative quarantines (95% CI 0.53–0.83), 33.59 million hospitalizations (22.41–39.31), and 0.62 million deaths (0.40–0.75) are expected in 365 days. The case fatality rate with pneumonia symptoms (moderate, severe and critical illness) is expected to be 1.83% (1.68–1.99%) and the infected fatality rate is 0.38‰ (0.33–0.4‰). The highest existing hospitalization and ICU occupations are 3.11 (0.30–3.85) and 20.33 (2.01–25.20) times of capacity, respectively. Sensitivity analysis showed that interventions can be adjusted to meet certain conditions to reduce the total number of infections and deaths. In conclusion, after sufficient respiratory and ICU beds are prepared and the relaxed NPIs are in place, the SARS-CoV-2 Omicron variant would not seriously impact the health system.     

SARS-CoV-2 evolves to reduce but not abolish neutralizing action

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) have prolonged coronavirus disease 2019 (COVID-19) pandemic by escaping pre-existing immunity acquired by natural infection or vaccination. Elucidation of VOCs' mutation trends and evasion of neutralization is required to update current control measures. Mutations and the prevalence of VOCs were analyzed in the global immunization coverage rate context. Lentivirus-based pseudovirus neutralization analysis platforms for SARS-CoV-2 prototype strain (PS) and VOCs, containing Alpha, Beta, Gamma, Delta, and Omicron, were constructed based on the spike protein of each variant and HEK 293T cell line expressing the human angiotensin-converting enzyme 2 (hACE2) receptor on the surface, and an enhanced green fluorescent protein reporter. Serum samples from 65 convalescent individuals and 20 WIBP-CorV vaccine recipients and four therapeutic monoclonal antibodies (mAbs) namely imdevimab, casirivimab, bamlanivimab, and etesevimab were used to evaluate the neutralization potency against the variants. Pseudovirus-based neutralization assay platforms for PS and VOCs were established, and multiplicity of infection (MOI) was the key factor influencing the assay result. Compared to PS, VOCs may enhance the infectivity of hACE2-293T cells. Except for Alpha, other VOCs escaped neutralization to varying degrees. Attributed to favorable and emerging mutations, the current pandemic Omicron variant of all VOCs demonstrated the most significant neutralization-escaping ability to the sera and mAbs. Compared with the PS pseudovirus, Omicron had 15.7- and 3.71-fold decreases in the NT50 value (the highest serum dilution corresponding to a neutralization rate of 50%); and correspondingly, 90% and 43% of immunization or convalescent serum samples lost their neutralizing activity against the Omicron variant, respectively. Therefore, SARS-CoV-2 has evolved persistently with a strong ability to escape neutralization and prevailing against the established immune barrier. Our findings provide important clues to controlling the COVID-19 pandemic caused by new variants.     

Safety and efficacy of olopatadine hydrochloride nasal spray for the treatment of seasonal allergic rhinitis to mountain cedar.

BACKGROUND: A nasal spray containing the antiallergy agent olopatadine hydrochloride is being developed for the treatment of seasonal allergic rhinitis (SAR) to mountain cedar. OBJECTIVE: To evaluate the safety and efficacy of 2 concentrations of olopatadine nasal spray vs placebo nasal spray in patients with SAR to mountain cedar. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. After a 3- to 21-day placebo run-in, 677 patients aged 12 to 81 years were randomized to receive 0.4% or 0.6% olopatadine or placebo, 2 sprays per nostril twice daily for 2 weeks. Patients evaluated morning and evening reflective and instantaneous nasal symptoms (sneezing, stuffy nose, runny nose, and itchy nose, which compose the total nasal symptom score [TNSS]) and ocular symptoms. RESULTS: Olopatadine spray (0.4% and 0.6%) was statistically significantly superior to placebo for percentage change from baseline in overall reflective and instantaneous TNSSs. Also, 0.6% olopatadine was statistically significantly superior to placebo for reducing the reflective and instantaneous assessments of sneezing, runny nose, itchy nose, stuffy nose, itchy eyes, and watery eyes. Olopatadine spray exhibited a safety profile comparable with that of placebo. CONCLUSIONS: Olopatadine nasal spray (0.4% and 0.6%) provided statistically significant improvements in allergic rhinitis symptoms compared with placebo regarding TNSSs and individual symptoms, including congestion, itchy and runny nose, sneezing, and itchy and watery eyes, in patients with SAR to mountain cedar. Olopatadine nasal spray administered twice daily was safe and well tolerated in adolescents and adults.     

Pre-exposure prophylaxis with tixagevimab and cilgavimab (Evusheld) for COVID-19 among 1112 severely immunocompromised patients

ObjectiveImmunocompromised patients have an increased risk of a severe form of COVID-19. The clinical efficacy of the tixagevimab/cilgavimab monoclonal antibody combination as pre-exposure prophylaxis against BA.1 and BA.2 SARS-CoV-2 Omicron sublineages is unknown. We aimed to describe the incidence and outcomes of COVID-19 among immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis during the Omicron wave in France.MethodsThis was an observational multicentre cohort study of immunocompromised patients receiving tixagevimab/cilgavimab as preexposure prophylaxis between December 28, 2021 and March 31, 2022. Patients received tixagevimab/cilgavimab 150/150 mg intramuscularly if they had impaired vaccine response and a high risk of severe form of COVID-19.ResultsTixagevimab/cilgavimab was administered to 1112 immunocompromised patients. After a median (range) follow-up of 63 (49–73) days, COVID-19 was confirmed in 49/1112 (4.4%) ≥5 days after treatment. During the study period, mean weekly incidence rate was 1669 in 100 000 inhabitants in Ile-de-France and 530 in 100 000 among patients who received tixagevimab/cilgavimab prophylaxis. Among infected patients, 43/49 (88%) had a mild-to-moderate form and 6/49 (12%) had a moderate-to-severe form of COVID-19. Patients with moderate-to-severe illnesses were less likely to have received early therapies than patients with mild forms (53.5% vs. 16.7% respectively) and 2/49 (4%) patients died from COVID-19.DiscussionOur study reported a low rate of infections and severe illnesses among immunocompromised patients treated with tixagevimab/cilgavimab. A global preventive strategy including vaccines, preexposure prophylaxis with monoclonal antibodies, and early therapies might be effective to prevent severe forms of COVID-19 among severely immunocompromised patients.